Leprosy, a chronic infectious disease affecting more than 12 million individuals today is caused by the intracellular pathogen Mycobacterium leprae. This organism is non-cultivatable, but recent work has shown that M. leprae will infect the nine-banded armadillo and the grey mangabey monkey. Additionally, M. leprae has been shown to undergo limited multiplication in the cooler body parts of rodents. A rodent model of leprosy, caused by Mycobacterium lepraemurium is also known. Both M. leprae and M. lepraemurium have been shown to be ingested by human and murine mononuclear phagocytes and to multiply within these cells in vitro and in vivo. The mechanisms by which phagocytic cells kill microorganisms is believed to include toxic oxygen intermediate production (H2O2, superoxide, hydroxyl radical) as well as lysosomal enzyme and bactericidal protein activity. Preliminary work in this laboratory and others has shown that although these mycobacteria are ingested they do not trigger a normal oxidative burst and appear to be resistant to lysosomal degradation. A clearer understanding of the mycobacteria-phagocyte interaction as well as the regulation of the phagocytic cell responses in leprosy will be crucial to the understanding and possible modification of this disease process. The objective of this investigation is to determine whether the failure of M. leprae and M. lepraemurium to stimulate phagocytic cell oxidative metabolism is influrenced by the opsonic and recognition conditions of the phagocyte-mycobacteria interaction or whether the organisms themselves actively suppress oxidative responses either directly or indirectly through modulation of phagocytic cell activation. One set of studies will determine complement activation and C3b binding by mycobacteria. Modulation of phagocyte FcR and C receptors by leprosy antigens and monoclonal antibodies will be used to study mycobacterial uptake and chemotactic responses of leprosy patient and normal control cells. In other studies with mycobacteria infected mice will be assayed for phagocytic cell oxidative responses and serum and spleen cell culture supernatants tested for suppressive activity toward normal cells. Patient and control cells will also be stimulated with various interleukins interferon, and macrophage products to determine if prior activation of the phagocytic cell can enhance or stimulate the oxidative metabolic burst when challenged with mycobacteria.